Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT04717622 |
| Other study ID # |
SOR-20-0287-CTIL |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
May 23, 2021 |
| Est. completion date |
March 2024 |
Study information
| Verified date |
October 2021 |
| Source |
Soroka University Medical Center |
| Contact |
Yael Yagel, MD |
| Phone |
972545385092 |
| Email |
ygrushka[@]gmail.com |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Zoonosis including brucellosis and rickettsial infections are a major contributor to
infectious morbidity in southern Israel. The Bedouins, a nomadic tribal population residing
in the Negev area are notably exposed to domesticated animals including livestock, camels and
companion animals, and their living conditions, especially with respect to poor sanitation in
different Bedouin communities also expose them to rodents and disease vectors such as insects
and arthropods. In this study, we aim to identify Bedouin patients arriving at the Soroka
University Medical Center, a tertiary hospital un the Negev, with undifferentiated fever,
suspected as a zoonosis.
We intend to use molecular methods to better diagnose the infectious agent using whole blood
and serum samples, and when available other tissues or body fluid, and use next generation
sequencing technology to deeply examine bacterial features such as virulence factors, and
host pathogen interactions.
Description:
This study aims to apply advanced technologies for the investigation of febrile illness in
the Bedouin population, in order to improve laboratory diagnosis in terms of rapidity and
sensitivity and to better our understanding of the pathophysiology of infectious diseases in
the Bedouin population including various environmental exposures such as animal, water and
waste and antibiotic exposure, as well as host-pathogen interactions associated with pathogen
virulence, factors associated with chronicity and relapse, and response to treatment.
Study protocol:
Enrollment:
1. After screening, patients will be approached and offered the opportunity to participate
in the study.
2. After signing of an informed consent patient will be interviewed and an enrollment
questionnaire will be filled out.
3. If the patient is enrolled in the ED, blood, saliva, and stool samples will be
collected. In case the patient presented with a rash or a skin lesion, a swab from an
open lesion will be obtained.
4. If patient was enrolled after receiving antibiotics, we will also attempt to locate
leftover blood samples that were drawn in the ED prior to receiving antibiotics.
Follow up:
- During hospitalization:
- Seven days after hospitalization or on day of discharge (whichever comes first), an
attempt will be made to obtain a second set of samples (blood, saliva, and stool),
and clinical data will be drawn from the medical records regarding resolution of
symptoms, antibiotic treatment, complications etc. In case of any surgical
procedures done during the hospitalization period for diagnostic or therapeutic
purposes (e.g. skin biopsy, bone biopsy, arthrocentesis, lumbar puncture), any
leftover material deemed unnecessary for clinical purposes will be utilized for
analysis.
- During the hospitalization, the patients will be interviewed and a WASH (Water,
Sanitation and Hygiene) questionnaire will be filled.
- Post-discharge ambulatory follow- up:
- In the case of a scheduled follow up visit in the infectious disease clinic (or any
other planned visit in the ambulatory service of SUMC), if blood sampling is
performed, an attempt will be made to obtain whole blood and serum samples for
research purposes. If study-designated blood sampling is not feasible, leftover
material will be utilized for research purposes. If deemed clinically relevant, a
follow up questionnaire will be filled out.
- Recurrent hospitalizations within the study period
o In case of recurrent admission during the year after enrolment, the hospitalization
will be assessed by the research team as "related" or "non-related" to the original
diagnosis. If considered related to the studied disease or its complications, an attempt
will be made to perform another blood sampling, and any leftover material from clinical
sampling of other body sites (biopsies, surgical intervention or drainage) will be
utilized for analysis. If deemed clinically relevant, a follow up questionnaire will be
filled out. As recurrent hospitalization are analyzed as part of the study, they will
not be considered serious adverse events (SAE).
- Six months after enrollment:
o Telephone interview for establishing clinical outcomes (protocol attached in
appendix).
- End of study period:
- One year post enrollment, data regarding antibiotic use, recurrent
hospitalizations, and long term complications will be collected from the patient's'
medical files.
Sample collection:
Every patient enrolled in this study will undergo the following workup:
Blood sampling:
Whole blood and serum samples will be obtained at enrollment, and if possible, upon discharge
and every planned ambulatory outpatient clinic visit or recurrent hospitalization. In case
that the patient was enrolled during hospital stay due to a positive test result, any
remaining leftovers from clinical non-research samples obtained prior to antibiotic
treatment, will potentially be used for research purposes, as long as they are not needed for
clinical use, and within the usual time frame of their storage in the relevant hospital lab.
Maximum blood volume obtained for analysis at each time point will be 10 ml for adults, and 5
ml for children.
Other clinical sampling:
At enrolment, saliva and stool samples will be obtained for microbiological analysis
including microbiome profiling, and any rash or wound sampling will also be analyzed by
molecular and metagenomic methods for the diagnosis of the culprit pathogen.
Sample processing and analysis:
All samples will be stored at the Moran-Gilad lab, Faculty of Health Sciences, Ben-Gurion
University of the Negev, for five years after enrolment. Processing of the samples will be
done in batches, and not in real time therefore, will not produce any real-time data that
could affect clinical decisions. The results of the analysis will not be available for the
treating physician. For the purpose of bacterial genomic/metagenomic sequencing, DNA will be
extracted from whole blood samples, and only microbial DNA will be identified and analyzed
from the extracted material. No research on human DNA will be performed in this study.
Bacterial isolates grown in standard cultures will be analyzed for further characterization
(e.g. virulence). Brucella or other bacterial isolates identified through standard cultures
will be further analyzed using in-vitro models including tissue culture for the analysis of
host-pathogen interactions. Immune response in clinical samples will be analyzed for host
inflammatory signals (e.g. gene expression, measurement of proteins). For the purpose of
improving diagnostic capability, specific PCR testing for zoonoses (such as Brucella,
Rickettsia, and Q fever, or others as needed) will be done on whole blood samples, attempting
to examine their utility and concordance with other means of diagnosis, and compared to
serological workup that will be performed using serum samples. All samples will be analyzed
according to proper biosafety level and good laboratory practices.
Meta-data collection and patient information All patients will be asked to fill a
questionnaire regarding the details of their current illness (attached in Hebrew and Arabic),
and their living conditions and exposure to animals.
Metadata including demographic data, health status, including chronic medical illnesses, and
prior hospitalizations, past history of zoonotic illnesses, will be collected from the
medical records. During hospitalization the following parameters will be collected: vital
signs including time till resolution of fever, lab testing and imaging results, and any
surgical procedure or intensive care unit stay.
Data will also be collected from the patient's medical records during the year following
enrollment to the study regarding factors associated with clinical outcomes including:
recurrent hospitalizations, antibiotic consumption, follow up blood test results such as
inflammatory markers, blood count, liver enzymes, and follow up serologic testing.
Study period and size This study aims to include a total of 500 patients, over three years,
starting September 2020.
Ethical considerations and data security All patients enrolled in the study will be assigned
a serial study number. All samples collected during this study will be labeled with the study
number, and no other identifying information will be present on the collected samples. Files
containing meta-data and questionnaires will also be labeled using study number. Informed
consent forms containing identifying data will be kept in a locked office accessed only by
the study team and a coding file matching identifying material with study numbers will be
saved on a password-protected server on hospital computers. Identifying data will be used for
the purpose of the follow-up phone interview at the end of the study period, and all
information obtained will then be de-identified and stored using the study code. All data
will be stored using REDCap secured web application.
